Short-term side effects of COVID-19 vaccines among healthcare workers: a multicenter study in Iran

Since the initiation of the COVID-19 vaccination effort, there has been widespread concern regarding vaccine efficacy and potential side effects. This study aimed to explore the short-term side effects of four available COVID-19 vaccines (Sputnik V, Sinopharm, Oxford–AstraZeneca, and Covaxin) among healthcare workers (HCWs) in Iran. The multicenter study involved 1575 HCWs, with the majority received Sputnik V (74.1%), followed by Covaxin (15.6%), Sinopharm (6.4%), and Oxford-AstraZeneca (3.8%). The prevalence of at least one side effect after the first and second dose COVID-19 vaccine was 84.6% and 72.9%, respectively. The common side effects (presented in > 50% of the study participants) after the first dose of the vaccine were injection site pain (61.7%), myalgia (51.8%), and muscle pain (50.9%). The most reported side effects after the second dose of the vaccine were injection site pain (26.8%), myalgia (15.8%), fever (10.3%), headache (9.9%), and chills (9.2%). In conclusion, according to the COVID-19 vaccine type, different side effects might occur following the first and second doses of vaccination. These findings assist in addressing the ongoing problems of vaccination hesitancy which has been driven by widespread worries about the vaccine safety profile.


Data collection
The study employed a structured questionnaire comprising three sections.The first part is about demographic information such as sex, age, medical history, the type of vaccination status against the COVID-19 vaccine, injection dates, and history of COVID-19 after vaccination.The second part focused on the general side effects of vaccines on several organ systems, including the skeletal, muscular, circulatory, digestive, neurological, and integumentary systems.Participants were requested to specify the onset and duration of each side effect following the first dose, second dose, or both doses of the vaccination.

Statistical analysis
Statistical analysis was performed using SPSS software version 20.0 (IBM SPSS Statistics for Windows, Armonk, NY: IBM Corp).Descriptive data were shown as numbers and percentages.Chi-square and Fisher's exact tests were used to find the association among the categorical variables and check the significance level at P value < 0.05.

Results
The study included 1575 healthcare workers (HCWs), with a predominant representation of females (78.5%).Table 1 provides a comprehensive summary of the participants' general demographic characteristics and medical history.The participants were categorized based on the age group: between 20 and 30 years old (n = 400, 25.4%); 30 and 40 years (n = 562, 35.7%); 40 and 50 years (n = 409, 26%); 50 and 60 (n = 179, 11.4%); and more than > 60 years of age (n = 25, 1.6%).The study shows the age group of 30-40 years in women and 40-50 years in men has the highest percentage.
Table 3 outlines the most common adverse effects associated with COVID-19 vaccines.The prevalence of side effects after the first and second doses was 75.6% and 71.8%, respectively.

Side effects after the first dose
Overall, the common side effects (presented in > 50% of the study participants) after the first dose of vaccine were injection site pain (61.7%) and myalgia (51.8%), while a moderately common side effect (presented in 30-50% of the study participants) were fever (43.4%), headache (38.2%), and chills (37.1%), respectively.Less common side effects, occurring in a few participants, involved tachycardia, dizziness, diarrhea, restlessness, chest pain,
Notably, no significant differences were identified in terms of sex, comorbidities, the time interval between contracting COVID-19 and receiving the vaccine, complications from the injection after the first and second doses, and post-vaccine COVID-19 infection (P value > 0.05).Furthermore, there was no significant association between the individual's comorbidities and vaccine complications after the first and second doses of the vaccine (P value > 0.05).

Sinopharm
Nearly one-third of the cases reported no side effects (35.3%).The most common adverse effects of the Sinopharm vaccine after injection were pain at the injection site (79.5%), and myalgia (26.1%).

Side effects after the second dose
Oxford-AstraZeneca Overall, the number of adverse events following the second dose of COVID-19 vaccination were lower than the side effects following the the first dose vaccination.A majority of cases (62.5%) reported no side effects following the second vaccine dose, with fever and myalgia reported in only 20.8% and 16.7% of cases, respectively.

Sputnik V
The most common adverse effects of Sputnik V vaccine after the second injection were myalgia (42.4%), and pain at the injection site (42.2%), with 25% of cases reported no side effects.

Covaxin
Second-dose adverse events following immunization with Covaxin were pain at the injection site (57.7%) and myalgia (45.5%), while 13.4% reported no side effects.

Sinopharm
Sixty percent of cases vaccinated with Sinopharm showed no adverse effects following the second injection.
Regarding the first dose vaccination, fever, nausea, chills, vomiting, headache, pain at the injection site, shortness of breath, cough, redness and inflammation, and myalgia were significantly associated with the Oxford-AstraZeneca vaccine (Table 3).On the other hand, side effects following the second dose vaccination, including fever, chills, and headache, were significantly associated with the Sputnik V vaccine, while headache, and myalgia were significantly associated with the Covaxin and Sputnik V vaccines, respectively.

Discussion
To the best of our knowledge, this study presents the most comprehensive analysis of the safety profile of COVID-19 vaccines in HCWs in Iran.All COVID-19 vaccines including Oxford-AstraZeneca, Sputnik V, Sinopharm, and Covaxin exhibited side effects particularly within the initial 24 h after vaccine administration.The prevalence of at least one side effect after the first and second dose of the COVID-19 vaccine was 84.6% and 72.9%, respectively.
Similar to previous studies, females were more likely to experience side effects than males.The higher frequency of side-effects among females can be explained by these biological mechanisms, intense cellular and humoral immune responses to vaccinations 11,12 .However, there is some reports that have reported higher side effects among males compared to females [13][14][15][16] .
The majority of these side effects manifested within 24 h following vaccination.Consistent with prior studies, fever, chills, headache, myalgia, tiredness, and pain at the injection site were identified as the most common after COVID-19 vaccinations 22,23 .In Xia et al. 24 study, injection site pain was the most common adverse reaction, followed by mild and self-limiting fever, with no noted severe adverse reactions.
Regarding the first dose vaccination, fever, nausea, chills, vomiting, headache, pain at the injection site, shortness of breath, cough, redness and inflammation, and myalgia were significantly associated with the Oxford-AstraZeneca vaccine.This aligns with previous reports that predominantly highlighted local and systemic side effects, particularly after the first dose of the Oxford-AstraZeneca vaccine 12,25,26 .
Consistent with other findings,, the adverse effects in the second dose were fewer than in the first dose 26 .Side effects following the second dose vaccination, including fever, chills, and headache were significantly associated with the Sputnik V vaccine, while headache and myalgia were significantly associated with the Covaxin and Sputnik V vaccines.
Notably, most of the adverse effects were observed following the first dosage of Oxford-AstraZeneca (95.1%), and there was an increased proportion of cases reporting no side effects after the second dose (62.5%).This elevated occurrence of adverse effects following the first dose of Oxford-AstraZeneca may indicate hesitancy towards receiving the second dose.Vaccine safety concerns [27][28][29] , including fears of potential side effects and a lack of trust in vaccine creation and distribution processes, have been reported as common reasons for HCWs to hesitate in accepting the COVID-19 vaccine 30 .
Approximately 15.1% and 27.1% of participants reported no side effects after the first dose and second dose of the COVID-19 vaccination, respectively.In the study reported by Jordanian HCWs, 18% and 31% of them reported no side effects following the first and second dose of the COVID-19 vaccination 25 .
In our study, a majority of HCWs (79.5%) had pain at the injection site following the first dose of the Astra-Zeneca vaccination.A study conducted in Ethiopia found that 75.8% of HCWs who received the AstraZeneca vaccine reported injection site symptoms 21 .Additionally, 55.6% of HCWs in our study reported developing a headache after receiving the AstraZeneca COVID-19 vaccine, consistent with findings in other studies 21,31 .The frequency of myalgia following the first-dose administration of AstraZeneca was 68.2%, which was higher than previous reports 21,25 .
In this study, the incidence of post-vaccine COVID-19 infection was higher than what has been reported in previous studies 16 .The effectiveness of the Oxford-AstraZeneca vaccine in preventing COVID-19 was reported to be 70.4%, and for Sinopharm, it ranged between 50 and 78% 25,31 .Several limitations should be acknowledged in our study.Firstly, the side effect profile was based on self-reported data, which introduces the potential for recall bias and subjective interpretation.Participants may not accurately recall or may perceive side effects differently, impacting the reliability of the reported information.Secondly, the study did not evaluate the severity of side effects, limiting our understanding of the intensity and impact of adverse reactions.Assessing the severity could provide a more comprehensive picture of the overall safety profile of the vaccines.Thirdly, the long-term effects of the observed side effects were not investigated in this study.Understanding the duration and persistence of adverse reactions is crucial for a comprehensive assessment of vaccine safety.Lastly, the absence of specific information regarding the identification, measurement, or control of potential covariates in the statistical analysis represents a limitation.This study did not explore the potential influence of pre-existing medical conditions or medications on the occurrence and severity of side effects.

Conclusion
The type of COVID-19 vaccine administered appears to influence the occurrence and nature of side effects following the first and second doses of vaccination.Our study indicates that the side effects associated with COVID-19 vaccines among HCWs were predominantly mild in severity.Notably, after the initial vaccination, Oxford-AstraZeneca, Sputnik V, and Covaxin resulted in a higher incidence of side effects, while the second dose of Sputnik V and Covaxin elicited more side effects.It is noteworthy that although a substantial frequency of adverse effects was noted following the first dose of Oxford-AstraZeneca (95.1%), a considerable proportion of individuals reported no side effects after receiving the second dose of the vaccine (62.5%).These findings contribute valuable insights to address the persistent challenges of vaccination hesitancy, which stem from widespread concerns about the safety profile of COVID-19 vaccines.

Table 2 .
Examining the frequency of different types of COVID-19 vaccines received with the time interval of side effects after the first and second doses of the vaccine.*P value < 0.05 has been considered significant.

Table 3 .
Side effects experienced after the first and second doses of COVID-19 vaccine.*P value < 0.05 has been considered significant.